Optical tweezers (OTs) are innovative instruments utilized for the manipulation of microscopic biological objects of interest. Rapid improvements in precision and degree of freedom of multichannel and multifunctional OTs have ushered in a new era of studies in basic physical and chemical properties of living tissues and unknown biomechanics in biological processes. Nowadays, OTs are used extensively for studying living cells and have initiated far-reaching influence in various fundamental studies in life sciences. There is also a high potential for using OTs in haemorheology, investigations of blood microcirculation and the mutual interplay of blood cells. In fact, in spite of their great promise in the application of OTs-based approaches for the study of blood, cell formation and maturation in erythropoiesis have not been fully explored. In this review, the background of OTs, their state-of-the-art applications in exploring single-cell level characteristics and bio-rheological properties of mature red blood cells (RBCs) as well as the OTs-assisted studies on erythropoiesis are summarized and presented. The advance developments and future perspectives of the OTs’ application in haemorheology both for fundamental and practical in-depth studies of RBCs formation, functional diagnostics and therapeutic needs are highlighted.
Despite extensive studies on different types of nanoparticles as potential drug carriers, the application of red blood cells (RBCs) as natural transport agents for systemic drug delivery is considered a new paradigm in modern medicine and possesses great potential. There is a lack of studies on the influence of drug carriers of different compositions on RBCs, especially regarding their potential impact on human health. Here, we apply conventional microscopy to observe the formation of RBC aggregates and optical tweezers to quantitatively assess the mutual interaction of RBCs incubated with inorganic and polymeric nanoparticles. Scanning electron microscopy is utilized for direct observation of nanoparticle localization on RBC membranes. The experiments are performed in a platelet-free blood plasma mimicking the RBC natural environment. We show that nanodiamonds influence mutual RBC interactions more antagonistically than other nanoparticles, resulting in higher aggregation forces and the formation of larger cell aggregates. In contrast, polymeric particles do not cause anomalous RBC aggregation. The results emphasize the application of optical tweezers for the direct quantitative assessment of the mutual interaction of RBCs influenced by nanomaterials.
Optical Tweezers (OT), as a revolutionary innovation in laser physics, has been extremely useful in studying cell interaction dynamics at a single-cell level. The reversible aggregation process of red blood cells (RBCs) has an important influence on blood rheological properties, but the underlying mechanism has not been fully understood. The regulating effects of low-level laser irradiation on blood rheological properties have been reported. However, the influence of pulsed laser irradiation, and the origin of laser irradiation effects on the interaction between RBCs remain unclear. In this study, RBC interaction was assessed in detail with OT. The effects of both continuous and pulsed low-level He–Ne laser irradiation on RBC aggregation was investigated within a short irradiation period (up to 300 s). The results indicate stronger intercellular interaction between RBCs in the enforced disaggregation process, and both the cell contact time and the initial contact area between two RBCs showed an impact on the measured disaggregation force. Meanwhile, the RBC aggregation force that was independent to measurement conditions decreased after a short time of pulsed He–Ne laser irradiation. These results provide new insights into the understanding of the RBC interaction mechanism and laser irradiation effects on blood properties.
The adhesion of red blood cells (RBC) has been studied extensively in frame of cell-to-cell interaction induced by dextran macromolecules, whereas the data are lacking for native plasma solution. We apply optical tweezers to investigate the induced adhesion of RBC in plasma and in dextran solution. Two hypotheses, cross-bridges and depletion layer, are typically used to describe the mechanism of cell interaction; however, both mechanisms need to be confirmed experimentally. These interactions in fact are very much dependent on the size and concentration of dextran and proteins in plasma. The results show that in different dextran solutions, the interaction of adhering RBC agrees well with the quantitative predictions obtained based on the depletion-induced cells adhesion model, whereas the migrating cross-bridges model is more appropriate for plasma. Despite the different mechanisms of RBC interaction in a mixture of dextran with the size ranges and volume fraction proportional to plasma proteins, the dependence of RBC adhering tends to be close to the cross-bridges model. The induced aggregation of RBC in the dextran solutions and in native plasma are observed by direct visualization utilizing scanning electron microscopy.
In the framework of novel medical paradigm the red blood cells (RBCs) have a great potential to be used as drug delivery carriers. This approach requires an ultimate understanding of the peculiarities of mutual interaction of RBC influenced by nano-materials composed the drugs. Optical tweezers (OT) is widely used to explore mechanisms of cells’ interaction with the ability to trap non-invasively, manipulate and displace living cells with a notably high accuracy. In the current study, the mutual interaction of RBC with polymeric nano-capsules (NCs) is investigated utilizing a two-channel OT system. The obtained results suggest that, in the presence of NCs, the RBC aggregation in plasma satisfies the ‘cross-bridges’ model. Complementarily, the allocation of NCs on the RBC membrane was observed by scanning electron microscopy (SEM), while for assessment of NCs-induced morphological changes the tests with the human mesenchymal stem cells (hMSC) was performed. The combined application of OT and advanced microscopy approaches brings new insights into the conception of direct observation of cells interaction influenced by NCs for the estimation of possible cytotoxic effects.
Optical tweezers (OT) is a unique Nobel Prize winning technology that has been widely used in studying cell interaction dynamics at a single-cell level with highly accurate manipulating of living cells and the ability to detect ultra-low intercellular forces. The reversible aggregation process of red blood cells (RBCs) that strongly influences the blood rheological properties thus being critical for blood microcirculation has long been research studied. However, in spite of plentiful researches dealing with RBC aggregation behavior based on an average response of a large number of cells, the detailed mechanism and the applicability of the two coexistent yet mutually opposed models to this reversible process require additional information. In this study, a two-channel optical tweezers system is utilized to reveal the influence of the cell interaction time (0-300 sec) on the RBC (dis)aggregation dynamics. The results show that for RBC enforced disaggregation in autologous plasma, the longer the two RBCs adhere to each other, the stronger the intercellular interaction is, and the lower the degree that a certain optical pulling force can separate two cells, whereas no significant effect of cell interaction time on RBC aggregation process was observed. This observation indicates that the RBC aggregation and disaggregation in autologous plasma are governed by different mechanisms and that the hysteresis effect, namely the dependence of the disaggregation force on RBC interaction history, is a significant feature that needs special consideration in researches related to the RBC disaggregation process.
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